<i>Saccharomyces cerevisiae</i>Dmo2p is involved in the mitochondrial copper metabolism and is required for the stability of newly translated Cox2p
Abstract Based on available platforms ofSaccharomyces cerevisiaemitochondrial proteome and other high throughput studies, we identified the yeast geneDMO2with a profile of genetic and physical interactions that indicate a putative role in mitochondrial respiration. Dmo2p is a homolog to human DMAC1 with two conserved cysteines in a Cx2C motif. Here, we localized Dmo2p in the mitochondrial inner membrane with the conserved cysteines facing the intermembrane space. The observed phenotypes of thedmo2null mutant indicate a general function in cellular stress response; the mutant displayed poor growth on non-fermentative media at 37°C, and in oleate, it is more sensitive to heat and oxidative stress while its overexpression confers resistance to some of the tested stressors. Dmo2p topology and modeled structure suggested a functional redox role for the Cx2C motif sustained by site-directed mutagenesis of both cysteine residues. The respiratory deficiency ofdmo2mutants at 37°C led to a reduction in cytochromecoxidase activity (COX) and the formation ofbc1-COX supercomplexes; we also observed a rapid turnover of Cox2p, the subunit two of the cytochromecoxidase complex that harbors the binuclear CuAcenter. Moreover, Dmo2p co-immunoprecipitated with Cox2p and components of CuAcenter maturation such as Sco1p and Sco2p; and finally,DMO2overexpression can suppresscox23respiratory deficiency, a mutant that has the mitochondrial copper homeostasis impaired. Overall, our data suggest that Dmo2p is required for Cox2p maturation, potentially by aiding proteins involved in copper transport and incorporation into Cox2p..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 27. März Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Soares, Maria Antônia Kfouri Martins [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/2023.06.12.544600 |
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| PPN (Katalog-ID): |
XBI039890430 |
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| 100 | 1 | |a Soares, Maria Antônia Kfouri Martins |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a <i>Saccharomyces cerevisiae</i>Dmo2p is involved in the mitochondrial copper metabolism and is required for the stability of newly translated Cox2p |
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| 520 | |a Abstract Based on available platforms ofSaccharomyces cerevisiaemitochondrial proteome and other high throughput studies, we identified the yeast geneDMO2with a profile of genetic and physical interactions that indicate a putative role in mitochondrial respiration. Dmo2p is a homolog to human DMAC1 with two conserved cysteines in a Cx2C motif. Here, we localized Dmo2p in the mitochondrial inner membrane with the conserved cysteines facing the intermembrane space. The observed phenotypes of thedmo2null mutant indicate a general function in cellular stress response; the mutant displayed poor growth on non-fermentative media at 37°C, and in oleate, it is more sensitive to heat and oxidative stress while its overexpression confers resistance to some of the tested stressors. Dmo2p topology and modeled structure suggested a functional redox role for the Cx2C motif sustained by site-directed mutagenesis of both cysteine residues. The respiratory deficiency ofdmo2mutants at 37°C led to a reduction in cytochromecoxidase activity (COX) and the formation ofbc1-COX supercomplexes; we also observed a rapid turnover of Cox2p, the subunit two of the cytochromecoxidase complex that harbors the binuclear CuAcenter. Moreover, Dmo2p co-immunoprecipitated with Cox2p and components of CuAcenter maturation such as Sco1p and Sco2p; and finally,DMO2overexpression can suppresscox23respiratory deficiency, a mutant that has the mitochondrial copper homeostasis impaired. Overall, our data suggest that Dmo2p is required for Cox2p maturation, potentially by aiding proteins involved in copper transport and incorporation into Cox2p. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Franco, Letícia Veloso Ribeiro |4 aut | |
| 700 | 1 | |a Chagas, Jhulia Almeida Clarck |4 aut | |
| 700 | 1 | |a Gomes, Fernando |4 aut | |
| 700 | 1 | |a Barros, Mário H. |0 (orcid)0000-0003-2977-9815 |4 aut | |
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